Use of albumin fusion technology to prolong the half-life of recombinant factor VIIa.
A significant proportion of patients with haemophilia A develop inhibitors to administered factor VIII (FVIII) and require therapy with bypassing agents such as activated factor VII (FVIIa) or activated prothrombin complex concentrates. NovoSeven is a commercially available recombinant FVIIa (rFVIIa) with a very short half-life of approximately 2.4 hours. As a result, patients generally require multiple, frequent infusions for the management of bleeding episodes. Thus, there is growing interest in extending the circulating half-life of coagulation factors through the use of innovative drug delivery and formulation technologies. One such approach uses albumin fusion technology in which human albumin is genetically fused to the C-terminus of rFVIIa via a flexible glycine serine linker. The properties of this rFVIIa fusion protein (rVIIa-FP) have recently been examined in pre-clinical studies. Results from these investigations demonstrate the feasibility of this approach, which successfully extended the half-life and biological activity of rFVIIa without compromising haemostatic efficacy. These data suggest that rVIIa-FP may be a promising therapy for the treatment of haemophilia patients with inhibitors and warrants further investigation in clinical trials.
Schulte
Stefan
S
CSL Behring GmbH, Emil-von-Behring Strasse 76, Marburg, Germany. Stefan.schulte@cslbehring.com
D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D015942:Factor VIIa / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology
D000418:Albumins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa